Several important questions relating to human health and disease are addressed in this proposal. Among the questions that are to be considered are: (1) The nature of the free radical reaction between lipids and molecular oxygen. The mechanism of this important process is being investigated with reference to health questions such as oxygen toxicity, carcinogenesis, aging, anaphylaxis, heart attack. (2) The nature of membrane control of small organic molecules. Membranes, being unusual media for organic molecules, may influence the conformation and stability of biologically important organic molecules and we intend to provide an understanding of this phenomenon at the fundamental level. (3) Free radical macrocyclization. We have discovered that large rings can be readily constructed by free radical addition and we intend to utilize this approach to develop methodology for construction of organic molecules. (4) Enzyme photoactivation. We intend to develop methods for photoactivation of an enzyme that will allow the inactive enzyme to be generated in its truly active form on a millisecond time scale. We will initially investigate the important enzymes of the blood clotting cascade since we have ready access to highly purified thrombin, factors IXa and Xa and we have a rational way of modifying these important enzymes. Our studies in these systems may well provide a valuable research tool in the study of blood clotting and in the long run may have chemical importance. The approach to all of these studies is at the level of organic mechanism. The rationale is to apply knowledge of mechanism to all of these problems to provide a new understanding of each system.